ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6349C>A (p.Gln2117Lys)

dbSNP: rs587780546
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002514592 SCV000153919 uncertain significance Familial adenomatous polyposis 1 2024-12-09 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 2117 of the APC protein (p.Gln2117Lys). This variant is present in population databases (rs587780546, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 132733). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health RCV000583428 SCV000687074 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-06 criteria provided, single submitter clinical testing This missense variant replaces glutamine with lysine at codon 2117 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has been identified in 1/250886 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences RCV000679079 SCV000805451 uncertain significance not provided 2017-11-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000583428 SCV001187301 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-15 criteria provided, single submitter clinical testing The p.Q2117K variant (also known as c.6349C>A), located in coding exon 15 of the APC gene, results from a C to A substitution at nucleotide position 6349. The glutamine at codon 2117 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Sema4, Sema4 RCV000583428 SCV002528641 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-30 criteria provided, single submitter curation
Baylor Genetics RCV002514592 SCV004203441 uncertain significance Familial adenomatous polyposis 1 2023-05-26 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003997302 SCV004840340 uncertain significance Classic or attenuated familial adenomatous polyposis 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces glutamine with lysine at codon 2117 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has been identified in 1/250886 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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